2018 – 2020 Funded Post-Doctoral Fellowship Projects
Discovering novel regulators of human totipotent stem cells.
Tatsuya Yamakawa, The Hospital for Sick Children ($150,000 for 3 years)
Supervisor: Janet Rossant
The advent of human pluripotent stem cells (hPSCs) has been a major breakthrough in understanding human development, modeling disease and developing new stem cell therapies. However, hPSCs are pluripotent not totipotent. Only the zygote and early stage blastomeres can be defined as totipotency as individual blastomeres have the ability to make all lineages including all three germ layers as well as the extraembryonic trophoblast and yolk sac, a property pluripotent stem cells do not have. The mechanisms underlying the molecular regulation of totipotency in the embryo remains largely unknown, especially in humans. There have been recent attempts to derive totipotent stem cells in both mice and humans. However, none have fully replicated the properties of the early totipotent embryonic cells and many attempts to make totipotent cells have tried to translate information from the mouse onto the human. Given the known differences between mouse and human in both timing and molecular details during preimplantation development, it is not surprising that previous studies have failed to make true human totipotent cells. This research project will use molecular information directly from the totipotent stages of human development to develop a screen for factors that can drive totipotent transformation from hPSCs. Establishment of human totipotent stem cells based on developmental knowledge will provide new insights into the totipotent state in human development and open up new possibilities in modeling human infertility and pregnancy problems.
2016 – 2019 Fellowships
Local ON/OFF control of tolerance toward allograft cell transplants
Jeffrey Harding, Lunenfeld-Tannenbaum Research Institute
Supervisor: Andras Nagy
Dissecting the role of Notch signaling during the transition from HE to HSC
Vladimir Manchev, University Health Network
Supervisor: Gordon Keller
2017-2019 (co-funded by Medicine by Design):
Rescuing vision in models of retinal degeneration
Project Leader: Arturo Ortin-Martinez, University Health Network (Valerie Wallace lab)
Developing an immune-cell approach to cardiac regeneration
Project Leader: Yiming Wang, University Health Network (Slava Epelman lab)
Other Current Funding:
New Ideas Grants
2018-2019 New Ideas Project Awardees
Elucidation of splicing-based mechanisms underlying cell fate control that represent targets in regenerative medicine applications
Benjamin Blencowe, University of Toronto ($75,000)
Alternative splicing (AS) is a regulatory process that allows a single gene to generate multiple different RNA transcripts and proteins. We have previously shown that specific AS events are critical for the control of embryonic stem cell (ESC) pluripotency, differentiation, and efficient reprogramming. However, the function of most AS events associated with these processes is not known. Our project aims to employ new methods to systematically define the roles of AS events in reprogramming and differentiation. This will be accomplished by applying a novel CRISPR-based screen we have developed to systematically delete genetic elements (i.e. alternative exons) to determine their role in controlling ESC pluripotency and neuronal cell differentiation. This method will be applied to ESCs, which will then be monitored for changes in pluripotency and neuronal differentiation-potential using high-throughput phenotyping assays. Furthermore, we will utilize another new CRISPR-based screen we have developed that employs dual-fluorescence splicing reporters to define combinations of regulators that can be manipulated to enhance reprogramming and neuronal differentiation. This research will establish generalizable, genome-wide approaches for the identification of exons and corresponding regulators of AS programs, and as such is expected to have broad utility in future research and therapeutic applications.
A matter of timing: how the circadian clock regulates intestinal regeneration.
Phillip Karpowicz, University of Windsor ($75,000)*
The human body has daily 24-hour cycles, known as circadian rhythms. Circadian rhythms are hardwired through a system of genes and hormones present in all the cells and tissues of the body. Shift-work, frequent travel, and artificial lighting can disturb circadian rhythms, and increase a number of serious illnesses. Our lab recently identified circadian rhythms in regeneration of the mouse small intestine. To better understanding this process, we will investigate circadian rhythms in both mouse and human organoids, artificial mini-organs grown in the lab from stem cells that can be used to model human diseases. Our study will investigate
a population of stem cells responsible for regeneration of intestinal tissue during injury and disease. Understanding circadian rhythm in organoid cultures will provide a timing for regeneration, and inform clinicians about the best time for therapeutic interventions. This knowledge could be applied to patients with inflammatory bowel disease or colorectal cancer, as well as patients treated by radiation or surgery.
Developing new reprogramming strategies for cell replacement therapy of glaucoma
Pierre Mattar, Ottawa Hospital Research Institute ($75,000)*
Glaucoma is a leading cause of blindness, with an estimated 400,000 Canadians affected. Glaucoma typically arises from an increase in intraocular pressure. Although often treatable, the buildup of intraocular pressure causes the death of retinal ganglion cells (RGCs), which are responsible for transmitting information from the eye to the brain. A large proportion of affected individuals are diagnosed too late to prevent RGC death, or progress to blindness despite treatment. Cell replacement therapy is a strategy that could potentially allow patients to recover their lost vision. Recent advances have demonstrated the promise of RGC transplantation for treating glaucoma. However, efficient generation of RGCs from patient-derived cells needs to be further developed in order to bring cell replacement therapy to the clinic. This project will use genetic tools to reprogram pluripotent stem cells towards RGCs as well as reprogram fibroblast cells directly into RGCs. This will lay the groundwork for future studies evaluating whether transplantation of RGCs produced in the laboratory can integrate into glaucomatous retinas and lead to functional repair.
Making new neurons from resident brain cells: a new therapy for stroke repair?
Maryam Faiz, University of Toronto ($74,946)*
Co-Investigator: Cindi Morshead, University of Toronto
Stroke is the leading cause of adult disability in Canada and the third leading cause of death. Current interventions are limited to restoring blood flow and preventing cell death during the acute phase following stroke. The need for novel therapies to promote plasticity and beneficial functional outcomes, including the regeneration of lost tissue, is clear. Reprogramming (the conversion of one cell type to another) offers one such possibility for neural repair after stroke, whereby reprogrammed cells would replace those lost to injury. Attempts at in vivo reprogramming in the brain have demonstrated successful conversion of astrocytes to neurons at the site of injury. However, the outcome of reprogramming in terms of functional recovery, the most clinically relevant measure of success, has not been examined. To address this gap, our research will investigate whether reprogramming of astrocytes to neurons improves the long-term disability caused by stroke.
Collaborative laboratory-based study of stem cell therapies: Preclinical Multicenter Acute lung injury Trials In Canada (PreMATIC)
Manoj Lalu, Ottawa Hospital Research Institute ($74,997)*
Dean Fergusson, Ottawa Hospital Research Institute
Bernard Thebaud, Ottawa Hospital Research Institute
Haibo Zhang, St. Michael’s Hospital
Ninety percent of ‘bench-to-bedside’ (i.e. preclinical-to-clinical) efforts fail to produce usable therapies. A lack of robust data from laboratories may be contributing these failures, since bench findings are often irreproducible and lack methodological rigor; a direct solution to this may be multicenter preclinical trials. Similar to clinical multicenter studies, a multicenter preclinical trial would overcome issues such as a lack of power and small sample sizes, and will account for heterogeneity of laboratories and personnel. Our team is interested in lung injury in patients with acute respiratory distress syndrome. Mesenchymal stromal cell derived exosomes (MEX) may be a novel therapy to help treat this condition. This project will use a multicenter preclinical trial approach to test the effect of MEX in a model of acute lung injury. Four laboratories in two centers will use harmonized protocols to induce lung injury and perform treatment with MEX. In order to generate precise estimates of efficacy, the study will employ methods to reduce risk of bias and will have a central analysis of outcomes. If exosomes prove beneficial, our study may lead to ‘cell-free cell-therapy’ in which MSC exosomes are administered in lieu of the whole cell. Our novel approach, will be the first multicenter preclinical study in Canada and the first multicenter evaluation of any stem cell product globally. Knowledge gained through this approach will allow a better understanding as to why preclinical-to-clinical translation has been riddled with failures.
Boosting cellular energy signals in muscle stem cells as a therapy for muscular dystrophy.
Keir Menzies, University of Ottawa ($75,000)*
Muscular dystrophy is a life-threatening muscular disorder, to which there is no cure. Part of the difficulty in treating this disorder is the fact that this is a genetic disease that affects a key protein, dystrophin, that maintains the structure of the muscle. Our project aims to examine the potential to alter the functional capacity of muscle stem cells (the cells responsible for muscle regeneration) to improve outcomes of patients with muscular dystrophy. Our research has previously found that hyper-activated proteins (PARPs) are responsible for a reduction in energy generation by the powerhouse of the cell, also known as the mitochondria. Extending our findings, we suspect that alterations in PARP activity leads to reduced energy function thereby disrupting muscle regeneration in muscular dystrophy. In this project, we will compare PARP activity in mouse models of muscular dystrophy to normal mice, to better understand the relationship on muscle stem cell function and regeneration. Through understanding of this family of proteins, we hope to design new therapies for muscular dystrophy.
2017-2018 Awardees (*co-funded by Medicine by Design; **Funded by Medicine by Design):
- The impact of environmental pollutants on pancreas development ($75,000) Project Leader: Jennifer Bruin (Carleton University)
- A 3D model of muscle to study potential therapies for Duchenne muscular dystrophy* ($75,000) Project Leader: Penney M. Gilbert (University of Toronto)
- Tailoring donor lungs to control immune response before transplant** ($75,000) Project Leader: Stephen C. Juvet (University Hospital Network)
- Improving the creation of bile duct cells to model liver disease** ($75,000) Project Leader: Binita M. Kamath (SickKids Research Institute)
- A computational modelling platform to support imaging and tissue design** ($75,000) Project Leader: John Parkinson (SickKids Research Institute)
- Understanding radial glial cell response to neural injury at a single cell level** ($75,000) Project Leader: Bret Pearson (SickKids Research Institute)
- A therapeutic strategy for treating Duchenne Muscular Dystrophy ($75,000) Project Leader: Michael A. Rudnicki (Ottawa Hospital Research Institute)
- Magnetic resonance imaging to assess stem cell treatments for lung diseasel** ($75,000) Project Leader: Giles Santyr (SickKids Research Institute)
- Autism spectrum disorder drug testing using human neurons ($75,000) Project Leader: Karun Singh (McMaster University)
- Clinical investigation of cell therapy to treat age-related osteoporosis ($75,000) Project Leader: William L Stanford (Ottawa Hospital Research Institute)
- Making new blood vessels for life-threatening lung diseases in newborns ($75,000) Project Leader: Bernard Thébaud (Ottawa Hospital Research Institute)
- New ways to stimulate the production of insulin-producing cells to treat diabetes* ($75,000) Project Leader: Michael B. Wheeler (University of Toronto)
Past Awardees (*co-funded by Medicine by Design):
- Control of immune tolerance toward allograft cell transplants ($50,000) Project Leader: Andras Nagy (The Lunenfeld-Tanenbaum Research Institute) 2015-16
- Dissolving scar tissue in spinal cord injuries improve candidacy and effects of stem cell transplants* ($49,988) Project Leader: Charles Tator (University Health Network) 2015-16
- Sole fuel source to enhance pluripotency ($50,000) Project Leader: Dean Betts (Western University) 2015-16
- An injectable biomaterial system for the delivery of stem cells in the treatment of retinal disease ($50,000) Project Leader: Heather Sheardown (McMaster University) 2015-16
- Activating enhancers to improve reprogramming efficiency* ($50,000) Project Leader: Jennifer Mitchell (University of Toronto) 2015-16
- Better maturation of iPS-derived heart cells ($49,200) Project Leader: John Coles (SickKids Research Institute) 2015-16
- Protein inactivation by agrochemicals as a mechanism underlying development of Autism Spectrum Disorder ($49,994) Project Leader: John Vessey (University of Guelph) 2015-16
- Injectable, tissue engineered scaffold for delivery of cardiac patches* ($50,000) Project Leader: Milica Radisic (University of Toronto) 2015-16
- Heart tissue repair via immune cell growth factors* ($50,000) Project Leader: Slava Epelman (University Health Network) 2015-16
- Intestinal stem cells and gut microbiota in early postnatal development and necrotizing enterocolitis ($49,980) Project Leader: Tae-Hee Kim* (SickKids Research Institute) 2015-16
- Biomimetic surfaces for directed differentiation of lung stem cells * ($49,983) Project Leader: Tom Waddell (Univerisity Health Network) 2015-16
- Mechanisms regulating differentiation in hemangioma stem cells ($49,500) Project Leader: Zia Khan (Western University) 2015-16
- TIMP-engineered niches for liver progenitor cell expansion ($75,000) Project Leader: Rama Khokha (University Health Network) 2014-15
- Control of RNA translation into proteins in human stem cells, neurons and disease ($75,000) Project Leader: James Ellis (SickKids Research Institute) 2014-15
- Engineering a functional human thymus from pluripotent stem cells ($75,000) Project Leader: Peter Zandstra (University of Toronto) 2014-15
- Role of short RNA fragments in mediating the anti-inflammatory effects of bone marrow stem cells in sepsis ($75,000) Project Leader: Duncan Stewart (Ottawa Hospital Research Institute) 2014-15
- Genomic correction of cardiac sarcomeric protein mutations in iPSC-derived cardiomyocytes ($75,000)Project Leader: John Coles (SickKids Research Institute) 2014-15
Other Current Funding:
OIRM’s research program includes large, disease-based team grants, smaller New Ideas Grants to answer basic research questions and Post-doctoral Fellowships.
2018-2019 Disease Team Awardees:
Towards a Cell Therapy Application Using Pluripotent Stem Cell-Derived Heart Muscle Cells to Regenerate Injured Hearts
Michael Laflamme, University Health Network ($370,000)
Graham Wright, University of Toronto
Gordon Keller, University Health Network
Ren-Ke Li, University Health Network
Terrence Yau, University Health Network
After myocardial infarction, “heart attack”, the heart muscle lost is replaced by non-contractile scar tissue, often initiating progressive heart failure. Our current options for treating post-infarct heart failure are limited, and it remains a disease with high morbidity, mortality and societal costs. The ability to “remuscularize” the infarct zone by transplanting cardiomyocytes, heart muscle cells, derived from human embryonic stem cells (hESCs) represents a potentially revolutionary new therapy for patients suffering from this disease. In order to treat the injured region a large number of cells are required. To address this, our team has translated protocols for the cardiac differentiation of hESCs from the lab bench to large-scale production, and we are now able to routinely generate hESC-derived cardiomyocytes in large cell batches. We have also developed improved protocols that guide the differentiation of hESCs into specialized cardiac subtypes, including the ventricular cardiomyocytes that are needed for infarct repair. This project will now perform proof-of-concept work to determine if the transplantation of hESC-derived ventricular myocytes can remuscularize the infarct scar and improve contractile function in a well-validated pig model of post-infarct heart failure. These studies will test the safety and efficacy of this novel cell therapy using endpoints including tissue structure, contractile function, as well as ECG recording and electrical function.
Cellular Immunotherapy for Septic Shock (CISS): Research to Move Stem Cells Through the Clinical Pipeline
Lauralyn McIntyre, Ottawa Hospital Research Institute ($370,000)
Shirley Mei, Ottawa Hospital Research Institute
Kednapa Thavorn, Ottawa Hospital Research Institute
Claudia dos Santos, St. Michael’s Hospital
Jason Acker, Canadian Blood Services
Dean Fergusson, Ottawa Hospital Research Institute
Septic shock is a devastating illness and the most severe form of infection seen in the intensive care unit (ICU). Approximately 20 – 40% of patients will die and survivors suffer significant long-term impairment in function and reduced quality of life. Despite decades of research examining different therapies, none has proven successful and supportive care remains the mainstay of therapy. Mesenchymal stem cells (MSCs) represent a novel treatment, and have been shown to modulate the immune system, increase clearance of bacterial pathogens, restore organ function, and reduce death in preclinical models. Our research team was the first in the world to have conducted and completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe and that a randomized controlled trial is feasible. Based on these results, we are now moving to a larger clinical trial at several academic hospitals across Ontario and Canada. This Phase II RCT (CISS2) will continue to evaluate safety, assess if there are strong signals for clinical benefit, and examine mechanisms and biological effects of MSCs. An economic analysis will also determine if the treatment is cost effective. This project will also focus on the optimization of a cryopreserved MSC product, identify bio-signatures tailored to septic shock to further identify potent cells, and to develop MSC modifications to further improve their performance characteristics for evaluation in future septic shock clinical trials.
Stem cell approaches to repairing damaged white matter in the brain of children and teenagers
Freda Miller, The Hospital for Sick Children ($370,000)
Donald Mabbott, The Hospital for Sick Children
Paul Frankland, The Hospital for Sick Children
David Kaplan, The Hospital for Sick Children
Cindi Morshead, University of Toronto
Douglas Munoz, Queen’s University
Jing Wang, Ottawa Hospital Research Institute
Ann Yeh, The Hospital for Sick Children
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. Our research project is focused on enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage.
Stimulating Muscle Repair for Duchenne Muscular Dystrophy
Michael Rudnicki, Ottawa Hospital Research Institute ($250,000)
Penney Gilbert, University of Toronto
Patrick Gunning, University of Toronto
William Stanford, Ottawa Hospital Research Institute
Jodi Chardon, The Ottawa Hospital
Hugh McMillian, Children’s Hospital of Eastern Ontario
Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease that affects 1/3500 boys that is characterized by progressive muscle wasting and premature death in the second or third decade of life. No effective cure-based therapy exists for DMD.Our research goal is to implement innovative therapeutic approaches for treating DMD patients to extend physical mobility and enhance quality of life by stimulating skeletal muscle regeneration using small molecule drugs. We believe that therapies targeting muscle stem cells to stimulate muscle regeneration can be combined with therapies to restore dystrophin expression to more effectively treat DMD. In this project, we will conduct the preclinical research necessary to bring innovative therapies to human clinical trials. We have identified a panel of small molecule drugs that improve the regenerative defect in DMD muscle stem cells. We will first test drugs on satellite stem cells that have been isolated from normal and dystrophic mice to confirm the drug activity and to determine the optimal dose. We will then treat normal and dystrophic models with drugs to test the effects and whether the drug enhances repair. Long-term experiments will be performed where drugs are given to dystrophic mice over several months to test whether drug treatment alleviates the dystrophic degeneration of muscle. These experiments will identify which drugs work best for preventing degeneration of dystrophic muscles. These promising drugs will be tested on human muscle stem cells to confirm that the drugs act on human cells in the same way they act on mouse cells. These muscles will be treated with candidate drugs to test whether muscle repair is enhanced. We will employ medicinal chemistry to explore optimization of lead candidates. Several of the drugs we are testing are human experienced, which could accelerate the pathway to clinical trial.
Generation and clinical use of white blood T-cells from stem cells for immune-regeneration and immunotherapy
Juan Carlos Zúñiga-Pflücker, University of Toronto, and Sunnybrook Research Institute ($250,000)
Donna Wall, The Hospital for Sick Children
T-cells are a subset of white blood cells that play a central role in immunity against infectious diseases and cancer. Unlike all other blood cells, which develop within the bone marrow (BM), T-cell development is dependent on migration of BM-derived progenitors to the thymus. However, thymus function can be severely damaged during radiation/chemotherapy and also deteriorates with age. While BM transplant is a potentially curative treatment for leukemia and other blood disorders, delayed T-cell recovery increases the risk of opportunistic infections and cancer relapse leading to high mortality rates. While some treatments appear to provide some level of protection to the thymus from the damage by radiation/chemotherapy, no method to date has been successful in increasing the likelihood of effective T-cell reconstitution or repairing thymic function. The goal of this proposal is the clinical translation of in vitro technology for the differentiation of hematopoietic stem cells into progenitor T-cells (proT) using a fully-defined and animal-free method. Our team will establish a cGMP compliant protocol based on our technology to produce a proT-cell clinical product that will be used to initiate a first in-human clinical trial validating the safety and efficacy of these proT cells in humans. This will lead to a better understanding how proT-cell infusions following hematopoietic stem cell transplantation (HSCT) can improve T-cell recovery and patient outcomes.
INCuBATOR: New Cell Treatments for Lung Injury in Babies – Getting research faster and safer into patients.
Bernard Thebaud, Ottawa Hospital Research Institute ($100,000)
Dean Fergusson, Ottawa Hospital Research Institute
Justin Presseau, Ottawa Hospital Research Institute
Kednapa Thavorn, Ottawa Hospital Research Institute
Extreme prematurity is the main cause of mortality and morbidity in children before 5 years of age. The most severe complication is bronchopulmonary dysplasia (BPD), a chronic lung disease that damages the lungs of preterm babies requiring a breathing machine and additional oxygen to stay alive. Because these injuries occur in developing organs, consequences are life-long and carry a high economic burden. Our lab was the first to show that umbilical cord-derived mesenchymal stromal cells (UC-MSC) could protect the lung from injury in neonatal laboratory models. UC-MSC has many advantages, especially for babies as the cells are easy to obtain after birth without harming mother or baby. These cells also have a higher repair capability and expansion potential. Our team has developed a new protocol that yields high numbers of low passage, GMP manufactured clinical grade UC-MSCs. In addition, our INCuBATOR approach will speed up the process of bringing this promising cell therapy into patients. In preparation for a Phase I human clinical trial, our team will perform several studies to: 1) ascertain that the cell product is safe and efficient through rigorous laboratory studies and reviews of research of others using a systematic analysis; 2) interview parents of preterm infants, physicians and researchers to obtain their views on the conduct of stem cell trials in babies and 3) conduct an economic evaluation to ensure that MSC therapy for BPD is economically viable. This information will help in designing the best possible clinical trial in babies. Thus, the INCuBATOR project will accelerate a potential breakthrough therapy that will improve the outcome of extreme preterm babies in Canada and world-wide
Cell transplantation to preserve central vision
Valerie Wallace, Krembil Research Institute ($100,000)
Andras Nagy, Lunenfeld-Tanenbaum Research Institute
Carol Schuurmans, SunnyBrook Research Institute
Molly Shoichet, University of Toronto
Derek van der Kooy, University of Toronto
Late stage retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative diseases that rob patients of central high acuity vision. The multiple underlying factors of these diseases converge on the loss of light sensitive cone photoreceptors in the central macular region of the retina, resulting in central vision loss. Rod photoreceptors and RPE are essential for the survival and function of cone photoreceptors. Current efforts to deploy cell-based retina repair strategies are hampered by several barriers, including a lack of efficient approaches to generate large numbers of therapeutic grade retinal cells for transplant. This project will develop an optimized procedure for the efficient induction and enrichment of human rod photoreceptors and RPE from stem cells and fibroblasts using small molecules and reprogramming strategies. Our group will develop and test novel biomaterials enhanced with photoreceptor survival factors and compare the survival and functional engraftment potential of single and combinatorial photoreceptor/RPE delivery on cone survival and function in animal models of late stage RP. This research will provide solutions for cell therapy safety and allograft immune tolerance.
What happens to cells injected in the knee of osteoarthritis patients?
Sowmya Viswanathan, Krembil Research Institute ($100,000)
Jas Chahal, Toronto Western Hospital
Ali Naraghi, University Health Network
Osteoarthritis (OA) is a common joint disease affecting 1 in 10 Canadians. It is a lasting condition in which cartilage breaks down, causing bones to rub against each other, resulting in stiffness, pain and loss of joint movement. Currently, there are few effective treatments available for patients suffering from osteoarthritis. MesenchymalStromal Cells (MSCs) are cells that can be obtained from bone marrow and other tissues. They reduce pain, inflammation and help with regenerating the cartilage. Although 18 global small clinical trials have been completed, questions regarding dose, timing of injection, route of administration and mechanism of MSCs still persist. Our research team has pioneered Canada’s OA trial using autologous MSCS. Early results show that the MSCs are safe, and have an effect in terms of pain and function. However, individual differences were observed between patients. There may be multiple reasons for these differences, including the quality and potency of the MSCs and their joint localization and interaction with local inflammatory cells. To address this gap in knowledge, this study will use a uniform, pre-selected MSC donor that is labelled with iron nanoparticles so they can be tracked once injected into patient knees by magnetic resonance imaging (MRI). This will tell us where the MSCs go in the joint, whether they to go to sites of inflammation, how many cells remain immediately, and a month after injection. Using this information, we can see how the localization and duration of MSCs in the joint correlates with the patient’s pain, quality of life, symptoms scores, and with changes in inflammation and inflammatory macrophages.
A trial to improve wound healing using stem cells from patient’s own discarded burned tissue.
Marc Jeschke, Sunnybrook Research Institute ($100,000)
The single most important factor that determines survival of a burn patient is wound healing. Our team recently isolated cells identified as burn-derived mesenchymal stem cells (BD-MSCs) from discarded burned skin. We then developed Integra®-SC a skin substitute that was engineered by incorporating BD-MSCs into Integra®, and found beneficial results in both small and large animal models. In this study, we will conduct a first-in-humans clinical trial at an academic hospital in Ontario. We will use Integra®-SC, developed from a patient’s own surgically removed burned tissue, to place on their excised burn wounds. We believe that Integra®-SC will facilitate and improve wound healing, heal faster, and, in the long-term, result in less scar formation. Utilizing Integra®-SC we can avoid surgically removing a patient’s own good uninjured skin to use as a donor tissue. After safety analyses, we will evaluate any needs or gaps in order to include recruitment of patients with a larger percent total body surface area burn. Integra®-SC has a broad clinical application and could impact the larger burn community, patients with traumatic and complex wounds, and the stem cell research community, creating a new standard for the way we care for patients in the province of Ontario and world-wide.
- A stem cell approach to regenerate the injured spinal cord ($400,000) Project Leader: Michael Fehlings (University Health Network)
- Cellular Immunotherapy for Septic Shock ($400,000) Project Leader: Duncan Stewart (Ottawa Hospital Research Institute)
- Towards a cell therapy application for using pluripotent stem cell-derived cardiomyocytes to treat cardiovascular disease ($250,000) Project Leader: Gordon Keller (University Health Network) –
- Cone photoreceptor derivation and transplantation – an innovative approach for the treatment of age-related macular regeneration ($250,000) Project Leader: Valerie Wallace (University Health Network) –
- Application of novel stem cell derived human non-monocytic dendritic cell precursors (hNM-DCPs) for immunotherapies ($250,000) Project Leader: Mick Bhatia (McMaster University)
- Preclinical evaluation of a bioengineered human islet ($100,000) Project Leader: Cristina Nostro (University Health Network)
- Overcoming central vision loss with stem cell therapy and rehabilitation ($100,000) Project Leader: Valerie Wallace (University Health Network
- Pluripotent and cord blood derived progenitor t-cells for immune reconstitution therapy ($100,000) Project Leader: JC Zuniga-Pflucker (Sunnybrook Research Institute)
Other Current Funding:
New Ideas Grants
OIRM supports four research-based programs, available to Ontario-based researchers and/or trainees.
OIRM Disease Team projects encompass large, collaborative research teams at multiple institutions across Ontario with potential partnerships outside the province. Disease Team grants support projects that are developing novel cellular or stem cell-related therapeutic approaches to tissue repair and regeneration for specific diseases. All OIRM Disease Teams are aimed at developing therapies with a clear path to the clinic. Grants are issued on an annual basis following a competitive, externally-reviewed process and are valued up to $750,000.
OIRM’s New Ideas program supports projects at the discovery level in the area of stem cell and regenerative medicine research. New Ideas projects are typically based at one institution with one or two investigators. The projects have clear and achievable short-term goals leading to clinical or commercial activities. Grants are issued on an annual basis following a competitive, externally-reviewed process and are valued up to $75,000.
The OIRM Fellowship Award supports outstanding trainees in basic research or health professions for up to three years to pursue a specific line of research in bioengineering, stem cells and/or regenerative medicine.
Trainee travel awards are available for qualifying applicants for OIRM supported workshops, events and conferences.
Non-OIRM funding opportunities are also posted to help support the research community.
New Idea Grants
KEY DATES FOR NEW IDEAS GRANTS
- June 1, 2018: Grant program launches
- June 29, 2018: Notice of Intent due
- November 2, 2018: Full grant application due
- November – January 2019: Review process
- March 2019: Funding announcement
- April 1, 2019: Funds are released
This grant competition is based on a 12-month funding period (April 1, 2019, to March 31, 2020) and is up to $75,000 CDN in value.
The New Ideas Grant will support projects at the discovery level in the area of stem cell and regenerative medicine research with a goal to foster cutting-edge research in stem cell biology and/or technology. The project can target:
- Basic molecular and cellular mechanisms underlying stem cell properties and behaviours;
- Stem cell or reprogrammed cell-based in vitro models to gain insight into disease mechanisms; or
- Stem cell or reprogrammed cell studies leading to novel therapies.
New Ideas Grant Application Package:
NEW IDEAS GRANT NOTICE OF INTENT APPLICATION FORM
NEW IDEAS GRANT GUIDELINES
NEW IDEAS GRANT APPLICATION FORM
NEW IDEAS GRANT BUDGET TEMPLATE
NEW IDEAS GRANT SIGNATURES FORM
Disease Team Grants
OIRM will not run an open Disease Team Grant competition for the 2019-2020 funding cycle. This competition will be limited to the nine currently funded teams.
OIRM Fellowship Award
Currently closed. Next competition opens October 2018.
Trainee Travel Awards
Till and McCulloch Meeting
OIRM is offering travel awards to help support trainees to attend the 2018 Till & McCulloch Meetings (TMM2018) in Ottawa, Ontario, November 12-14, 2018. Travel awards will be given to top-ranking abstracts as ranked by the TMM abstract committee. To be eligible OIRM trainees must submit their abstract to TMM by the July 11, 2018 abstract deadline. Click here for abstract details and to register.
Non-OIRM Funding Opportunities
Funding Amount: $97,500 per year for up to 3 years
Application Deadline: June 15, 2018
Open to International Organizations
Funding Opportunity #W81XWH18PRMRPCTA
Funding Amount: Unrestricted
Pre-Application Submission Deadline: June 25, 2018
Open to International Organizations
Funding Opportunity #W81XWH-18- MSRP-IIRA
Funding Amount: up to $600,000
Pre-Application Submission Deadline: June 26, 2018
Funding Amount: up to $95,000 USD per year for up to 3 years
Application Deadline: June 26, 2018
Funding Amount: up to $200,000 over up to 18 months
Application Deadline: August 1, 2018
Funding Amount: up to $1,500,000 over up to 3 years
Application Deadline: August 1, 2018
Funding Amount: $70,000 per year for up to 2 years
Application Deadline: September 19, 2018
OIRM is a network of 1700+ stem cell biologists, bioengineers, clinicians, industry and business leaders and their trainees working within stem cell and regenerative medicine in Ontario. With members located in nine cities across the province, we are a community that supports collaboration between labs and across disciplines to advance both basic research and clinical translation.
- Members must hold a primary, full-time faculty appointment at an Ontario University or affiliated Research Institute
- Members require a PhD and/or MD in a scientific field appropriate to stem cell and regenerative medicine research
- Members require at least two published academic papers in the field of stem cell and regenerative medicine; for clinicians, a strong interest in regenerative medicine approaches in their area of clinical expertise can act as a substitute
As a member of our community, you and your trainees have access to many resources and programs to help support your research. OIRM member benefits include:
You are an important member of this community and as a member of OIRM, we encourage you be active members of the community, through your own participation in OIRM activities and by encouraging your trainees to attend our education talks and workshops. Because the strength of the community is built upon its scientists, OIRM members may be called upon to provide talks, engage with the public and become advocates for the OIRM’s programs and opportunities. Download our membership benefits document.
If you meet the above criteria and are willing to be an active part of our community, please provide the following documentation to email@example.com
- A one-paragraph statement on official letterhead explaining why you would like to be a member of OIRM and how our network can benefit your research
- Updated CV, highlighting publications in the field of stem cell and regenerative medicine
After an internal review, those approved, will be added to our “OIRM Scientists” webpage. To complete your profile you will be asked to provide the following information;
- link to your university profile
- link to your hospital/research institute profile
- one paragraph on your research interests
- link to your PubMed listing
- five key words to describe your research
- a high-resolution photo (head shot)
- admin contact info (if applicable)
- a list of trainees and email addresses
For more information about OIRM membership, our membership benefits or to apply please contact Jodi.firstname.lastname@example.org.